A major objective of the Monoclonal Antibody/Hybridoma Section is the production of murine monoclonal antibodies to human tumor-associated antigens. For this purpose, we have employed human colorectal cancer as a system for testing the efficacy of new and present methods of elicitation. We have found that membrane peripheral protein extracts of human colorectal cancer from heterotransplants combined with Sepharose-insolubilized lectins was far more efficient in eliciting antibodies to TAA. As a result, we are presently extensively evaluating six antibodies by histochemical and molecular techniques. A second major emphasis in evaluation of monoclonals is directed towards methods and assays which allow for selection of diagnostic and therapeutically useful antibodies. This second level of evaluation is exemplified by two monoclonal antibody-defined human melanoma-associated antigens, one of 100K daltons, the other of 250K daltons. The 100K dalton antigen levels in melanoma patients' sera correlated with tumor burden and 9.2.27 antibody to the 250K glycoprotein was effective in treatment of established human melanoma in nude mice. A third level of evaluation of monoclonal antibodies is related to their therapeutic efficacy in patients. Ongoing laboratory studies, in coordination with a clinical trial within the Clinical Investigations Section, are presently assessing humoral and cellular responses to administered monoclonal antibody, antibody localization in tumor and normal tissues and the histopathological examination of tumor nodules for evidence of antigenic heterogenity. These levels of evaluation indicate a continuing improvement in the ability to elicit, select, and evaluate monoclonal antibodies for clinical utility, and to use them as probes in basic studies on the nature of tumor-associated antigens.